In the present study, the objective was to attain a localized lung delivery of an anti-tubercular fluoroquinolone, moxifloxacin (MXF), targeting the alveolar macrophages through a non-invasive pulmonary route using inhalable microspheres as a dry powder inhaler approach. MXF-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres (MXF-PLGA-MSs) were fabricated by solvent evaporation technique and optimized by using a central composite statistical design. The morphology and particle size, as well as the flowability of the optimized microspheres, were characterized. In addition, the aerosolization performance of the optimized formula was inspected using an Andersen cascade impactor. Furthermore, in vivo fate following intrapulmonary administration of the optimized formula was evaluated. The optimized MXF-PLGA-MSs were spherical in shape with a particle size of 3.16 µm, drug loading of 21.98% and entrapment efficiency of 78.0%. The optimized formula showed a mass median aerodynamic diameter (MMAD) of 2.85 ± 1.04 µm with a favorable fine particle fraction of 72.77 ± 1.73%, suggesting that the powders were suitable for inhalation. Most importantly, in vivo studies revealed that optimized MXF-PLGA-MSs preferentially accumulated in lung tissue as manifested by a two-fold increase in the area under the curve AUC_0–24h, compared to plain drug. In addition, optimized MXF-PLGA-MS sustained drug residence in the lung for up to 24 h following inhalation, compared to plain drug. In conclusion, inhalable microspheres of MXF could be a promising therapeutic approach that might aid in the effective eradiation of tuberculosis along with improving patient adherence to the treatment.

中文翻译：

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可吸入性莫西沙星微球的肺靶向治疗可有效治疗肺结核

在本研究中，目的是通过使用吸入性微球作为干粉吸入器方法，通过非侵入性肺部途径将抗结核性氟喹诺酮类药物莫西沙星（MXF）靶向肺泡巨噬细胞。通过溶剂蒸发技术制备了载有MXF的聚乳酸-乙醇酸（PLGA）微球（MXF-PLGA-MS），并使用中央复合统计设计对其进行了优化。表征了优化的微球的形态和粒径以及其流动性。另外，使用安德森（Andersen）级联冲击器检查了优化配方的雾化性能。此外，评价了优化配​​方的肺内给药后的体内命运。经过优化的MXF-PLGA-MS为球形，粒径为3.16 µm，载药量为21.98％，包封率为78.0％。优化的配方显示质量中位数空气动力学直径（MMAD）为2.85±1.04 µm，有利的细颗粒分数为72.77±1.73％，表明这些粉末适合吸入。最重要的是，体内研究表明，优化的MXF-PLGA-MS优先在肺组织中积累，表现为曲线AUC下面积增加了两倍。与普通药物相比_0-24小时。此外，与普通药物相比，优化的MXF-PLGA-MS在吸入后可将药物在肺中的停留时间长达24小时。总之，MXF的可吸入微球可能是一种有前途的治疗方法，可以有效地根除结核病并改善患者对治疗的依从性。